The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis.
Fibrosis is a pervasive disease in which the excessive deposition of extracellular matrix (ECM) compromises tissue function. Although the underlying mechanisms are mostly unknown, matrix stiffness is increasingly appreciated as a contributor to fibrosis rather than merely a manifestation of the disease. Here we show that the loss of Fibulin-5, an elastic fibre component, not only decreases tissue stiffness, but also diminishes the inflammatory response and abrogates the fibrotic phenotype in a mouse model of cutaneous fibrosis. Increasing matrix stiffness raises the inflammatory response above a threshold level, independent of TGF-β, to stimulate further ECM secretion from fibroblasts and advance the progression of fibrosis. These results suggest that Fibulin-5 may be a therapeutic target to short-circuit this profibrotic feedback loop.
Duke Scholars
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- Transcription Factors
- Snail Family Transcription Factors
- Skin
- Recombinant Proteins
- Phenotype
- Middle Aged
- Mice, Transgenic
- Male
- Inflammation
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Transcription Factors
- Snail Family Transcription Factors
- Skin
- Recombinant Proteins
- Phenotype
- Middle Aged
- Mice, Transgenic
- Male
- Inflammation
- Humans